THE WOODLANDS, Texas—More than 30 million women of reproductive age in the United States are afflicted with symptomatic uterine fibroids or endometriosis, according to Repros Therapeutics Inc. More than 300,000 hysterectomies are performed in this country every year to treat those two disorders. The National Uterine Fibroids Foundation estimates that 80 percent of all women in the U.S. have uterine fibroids, and one in four of these women have symptoms severe enough to require treatment.
Because no acceptable chronic therapeutic options are available today, the current standards of care for uterine fibroids and endometriosis consist of surgery or short-term treatment with gonadotropin-releasing hormone (GnRH) agonist drugs. GnRH agonists, which induce a low-estrogen, menopausal-like state and promote bone loss, are not recommended for use for more than six months.
Repros, which began in 1987 as Zonagen to try to develop birth-control methods based on modification of the zona pellucida (a part of the oocyte), may have some answers to these female issues. Today Repros is a development-stage biopharmaceutical company that focuses on the development of new drugs to treat hormonal and reproductive system disorders, and one of the compounds it has developed is Proellex, a chemical entity that acts as a selective blocker of the progesterone receptor. It could have potential for the treatment of symptoms associated with uterine fibroids and endometriosis, the company says. Currently, there are no FDA-approved, orally administered drugs for the long-term treatment of either uterine fibroids or endometriosis, but this may potentially change with the FDA having accepted an Investigational New Drug Application for vaginally delivered Proellex.
In April, Repros reported that vaginal administration of Proellex at doses of both 6 mg and 12 mg achieved significant reduction in excessive menstrual bleeding, the key symptom of uterine fibroids. A small Phase 2b study showed that when a sufficient concentration of Proellex is achieved in circulation, amenorrhea (cessation of menses) is achieved. Just over half of Proellex-treated subjects (52 percent) became amenorrheic with no evidence of a dose effect. All subjects treated with placebo continued to menstruate throughout the 18-week dosing period. There was a statistically significant difference in the number of days of bleeding and bleeding intensity between those treated with Proellex and placebo.
Along with changes in menstrual patterns, fibroids measured by MRI were reduced in volume in the Proellex-treated arms by 18 percent, while the placebo group showed continued increase in size. The drug was generally well tolerated. Women in the drug arms continued to exhibit levels of estradiol consistent with bone preservation.
After the first 18-week treatment period, the women were withdrawn from drug to allow for menses. The women in the study are currently being treated with the second course of treatment for another 18 weeks. The results of the second course of treatment should be reported within the next five months.
In May, Repros reported that oral administration of Proellex at doses of both 6 mg and 12 mg achieved significant reduction in excessive menstrual bleeding, the key symptom of uterine fibroids. Additionally, fibroids were reduced, and evidence of bone growth was observed.
Once both the vaginal and oral studies complete both 18-week courses of treatment, the company plans to request an end of Phase 2 meeting with the FDA to jointly discuss plans for Phase 3.
Patrick Fourteau, who recently accepted the position of chairman on the board of Repros, stated, “I am delighted to become chairman of Repros during this important period. In Proellex the company has an asset that can improve lives and whose potential commercial value must be carefully assessed.”